Cell Body and Genetics of Aging

Aging

Which mitochondrial respiratory complex is the major source of ROS production?

Complex III (CoQH₂-cytochrome c reductase)

Which enzyme restores lost telomere ends and can lead to immortalization when upregulated?

Telomerase

What is the biological significance of apoptosis?

Eliminates B- and T-cells that fail proper antigen recognition

Segmental progeroid syndromes

accelerate some but not all features of aging 

The loss of contact inhibition in cells is most directly associated with

Cancer/tumor formation

What is a proven effect of caloric restriction in animal models?

Increased lifespan and reduced DNA damage

Define caloric restriction and explain its relationship to ROS production and DNA damage.

Caloric restriction = reduced calorie intake without malnutrition; lowers ROS production from mitochondria, reduces oxidative DNA damage, increases longevity.

List major types of oxidative DNA lesions caused by ROS.

DNA base modifications (8-oxoG)

single- or double-strand breaks

interstrand cross-links.

Describe the structure of telomeres and explain how they protect chromosomes.

Telomeres are TTAGGG repeats forming a hairpin loop that caps chromosome ends, preventing degradation and fusion.

Name one genetic disease associated with accelerated aging and its genetic defect

Hutchinson-Gilford Progeria Syndrome (HGPS) caused by A-type lamin mutation; leads to rapid aging.

Explain the difference between cellular senescence and immortalization

Cellular senescence = irreversible cell-cycle arrest after damage/telomere shortening; Immortalization = unlimited division (often via telomerase activation).

Why is apoptosis crucial for immune system function?

Apoptosis removes autoreactive or nonfunctional lymphocytes during immune cell maturation, maintaining immune tolerance.

Describe what happens when telomere length becomes critically short.

Critically short telomeres expose chromosome ends, triggering DNA damage responses, genomic instability, and senescence or apoptosis.

Briefly explain how HeLa cells have been used in medical research.

HeLa cells (immortalized cervical cancer cells) are widely used for vaccine production (e.g., polio, HPV) and biomedical research.

Telomerase 

Restores telomere ends, often upregulated in cancer

Complex III

Major source of mitochondrial ROS

Contact inhibition

Stops cell proliferation when cells are too crowded

Progeria (HGPS)

Caused by A-type lamin defect; rapid aging phenotypes

Apoptosis

Programmed cell death important for immune selection 

How might excessive ROS production from mitochondria lead to cancer formation as well as aging?

ROS can damage DNA, causing mutations that promote cancer; accumulated damage also contributes to cellular senescence and loss of function with age.

If a drug could safely extend telomere length in somatic cells, what are the potential benefits and risks?

Benefits: extended regenerative capacity and delayed senescence.

Risks: higher cancer risk due to immortalization of precancerous cells.

Explain why progeroid syndromes are useful for understanding normal aging despite not replicating all aging features

Progeroid syndromes model accelerated aging, allowing scientists to study mechanisms like DNA repair, nuclear structure, and gene expression that also play roles in normal aging.